Is RAB34 p.Arg231Ter (c.691C>T) pathogenic?

RAB34 p.Arg231Ter (c.691C>T) is classified Likely pathogenic in RAB34 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-27). Ultra-rare (popmax 0.0245%, eas); Associated with Jeune syndrome.

What condition is associated with RAB34 p.Arg231Ter (c.691C>T)?

RAB34 p.Arg231Ter (c.691C>T) is associated with Jeune syndrome, orofaciodigital syndrome 20 (ClinVar).

How common is RAB34 p.Arg231Ter (c.691C>T) in the general population?

RAB34 p.Arg231Ter (c.691C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

RAB34 p.Arg231Ter

c.691C>T · rs757465924 · VCV2506967

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (9 of 10, 21 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,896 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00167% 27/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,081
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00127%	78,669

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RAB34
Protein: p.Arg231Ter
Coding: c.691C>T
MANE Select: NM_031934
dbSNP: rs757465924
Type: single nucleotide variant
Location: chr17:28714814 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.94
Residue 231: a UniProt-annotated variant site (in ofd20; likely pathogenic)

Full RAB34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Jeune syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: orofaciodigital syndrome 20

Similar variants

RAB34 p.Ile85Thr Likely pathogenic ★ same condition
RAB34 p.Gly202Val Uncertain significance ★ ⚠ same condition
RAB34 p.Arg211His Pathogenic same condition
RAB34 p.Glu218Lys Pathogenic same condition
RAB34 p.Glu153del Uncertain significance ★ same condition
RAB34 p.Ala213Gly Uncertain significance ★ ⚠ same type
RAB34 p.Ala213Ser Uncertain significance ★ ⚠ same type
RAB34 p.Arg123Lys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rab34-p-arg231ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown